This proposal requests funds to purchase a multi-photon confocal microscope system integrated with a Ti:sapphire laser, an upright fluorescence microscope, and an electrophysiological set-up. Eleven separate NIH-funded laboratories (from 4 of the 5 basic research departments and 3 clinical departments at New York Medical College and Cornell University Medical College) have proposed experiments using this instrument. These projects include 1) assessing the role of astrocytic calcium signaling in synaptic transmission and ischemic brain injury, 2) evaluating dendritic and axonal calcium spikes in hippocampal and tegmental neurons, 3) visualization of the cell-cell interactions that permit the migration of new neurons generated from the subependyma of the adult brain, as identified by cell-specific, GFP-expressing adenoviral vectors, 4) imaging of GFP-expressing glioma cells during their invasion into host brain, and 5) analysis of apoptosis in several systems, include retina, myocardium, and tumors. These experiments will take advantage of the ability of the two-photon confocal microscope system to 1) image deep into live tissue, 2) image for extended time periods with minimal tissue damage, and 3) focally uncage molecules in small regions inside and outside cells. The multi-photon confocal microscope system will become a core facility at New York Medical College, serving the entire medical science community.